Trial of Dasatinib in Advanced Sarcomas

• Sponsor: Sarcoma Alliance for Research through Collaboration (Other)
• Overall Status: Completed
• CT.gov ID: NCT00464620
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 366
• Locations: 20
• Arm: 1
• Duration (Months): 120
• Patients Per Site: 18.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will examine the response rate and the 6-month progression-free survival rates of subjects with advanced sarcoma treated with dasatinib.

Condition or Disease	Intervention/Treatment	Phase
Rhabdomyosarcoma; Malignant Peripheral Nerve Sheath Tumors; Chondrosarcoma; Sarcoma, Ewing's; Sarcoma, Alveolar Soft Part; Chordoma; Epithelioid Sarcoma; Giant Cell Tumor of Bone; Hemangiopericytoma; Gastrointestinal Stromal Tumor (GIST)	Drug: Dasatinib	Phase 2

Detailed Description

Further details provided by SARC (Sarcoma Alliance for Research through Collaboration):

Treatment: Subjects take Dasatinib twice daily by mouth for 28 days per 28 day cycle.

Subjects will be seen for interim medical history, physical exam and laboratory studies prior to each cycle. Subjects will undergo tumor imaging every 2 months (8 weeks) for the first 6 months and approximately every 3 months thereafter while on treatment.

A blood sample for collection of specimens with which to later study serum level of Dasatinib and effects on biomarkers of drug activity will be obtained approximately 2 to 4 weeks after the start of treatment.

Central collection of archival tumor with which to later study the frequency of expression and/or mutation of kinases inhibited by dasatinib will occur.

Subjects will be followed for approximately every 3 months until 2 years from registration and then approximately yearly until 5 years from registration.

Study Design

• Study Type: Interventional
• Actual Enrollment: 366 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Dasatinib in Advanced Sarcomas
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dasatinib, 70 mg, twice daily Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles	Drug: Dasatinib; oral agent, continuous dosing, Cycles = 28 days

Outcome Measures

Primary Outcome Measures

1. Response Rate: Number of Participants With Objective Tumor Response [Up to 24 months]

   Assessment of objective tumor response for response rate with MRI or CT using Choi criteria: Complete Remission (CR) Complete disappearance of all measurable and evaluable disease for at least 4 weeks; Partial Remission (PR) A 10% or greater decrease from the baseline in the sum of the largest diameters of all measurable target lesions.

2. 6 Month Progression-free Survival Rate of "Indolent" Sarcomas Treated With Dasatinib [At 6 months]

   Estimate the 6 month progression-free survival rate of "indolent" sarcomas treated with dasatinib. Progression is defined using Choi criteria, as a 10% or greater increase in the sum of all measurable target lesions over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or unequivocal reappearance of any lesion which had disappeared, or appearance of any new lesions of greater than double slice thickness in size, or any new or enlarging solid nodule in a previously hypodense treated mass.

3. 6 Month Progression-free Survival Rate of Gastrointestinal Stromal Tumors (GIST) [6 months]

   To estimate the 6 month progression-free survival rate of gastrointestinal stromal tumors (GIST). Progression is defined using Choi criteria, as a 10% or greater increase in the sum of all measurable target lesions over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or unequivocal reappearance of any lesion which had disappeared, or appearance of any new lesions of greater than double slice thickness in size, or any new or enlarging solid nodule in a previously hypodense treated mass.

Secondary Outcome Measures

1. Median Time-to-progression of Subjects With GIST Treated With Dasatinib. [Up to 30 months]

   To estimate the median time-to-progression of subjects with GIST treated with dasatinib.

2. Overall Survival Rates at 2 and 5 Years From Registration of Subjects Treated With Dasatinib. [At 2 and 5 years]

   To estimate the overall survival rates at 2 and 5 years from registration of subjects treated with dasatinib.

3. Median Time-to-progression of Subjects With "Indolent" Sarcomas Treated With Dasatinib. [Up to 24 months]

   To estimate the median time-to-progression of subjects with "indolent" sarcomas treated with dasatinib.

4. 6 Month Progression-free Survival Rate of Subjects Enrolled in the Aggressive Subtype. [At 6 months]

   To estimate the 6 month progression-free survival rate of subjects with leiomyosarcoma, liposarcoma, osteosarcoma including high-grade chondrosarcomas, Ewing's sarcoma, Malignant fibrous histiocytoma (MFH), rhabdomyosarcoma and MPNST treated with dasatinib.

5. Median Time-to-progression of Subjects Enrolled in the Aggressive Subtype. [Up to 37 weeks]

   To estimate the median time-to-progression of subjects with leiomyosarcoma, liposarcoma, osteosarcoma including high-grade chondrosarcomas, Ewing's sarcoma, MFH, rhabdomyosarcoma and MPNST treated with dasatinib.

6. Overall Survival Rates at 2 and 5 Years From Registration of Subjects Enrolled in the Aggressive Subtype Treated With Dasatinib. [At 2 and 5 years]

   To estimate the overall survival rates at 2 and 5 years from registration of subjects enrolled in the aggressive subtype treated with dasatinib.

7. Uni-dimensional and Bi-dimensional Tumor Size, Tumor Volumes and Tumor Average Density Determined by Computer-aided Automated Detection in a Subset of Subjects With Tumor Predominately Involving the Lung [Up to 37 weeks]

   To prospectively collect uni-dimensional and bi-dimensional tumor size, tumor volumes and tumor average density determined by computer-aided automated detection in a subset of subjects with tumor predominately involving the lung

8. Plasma Level of Dasatinib and Inhibition of SRC and/or Focal Adhesion Kinase (FAK) in Peripheral Blood Mononuclear Cells [2-4 weeks from start of treatment]

   Obtain blood samples to characterize plasma level of dasatinib and inhibition of SRC and/or FAK in peripheral blood mononuclear cells 2 hours after ingestion of drug at 2-4 weeks from the start of treatment if activity of the drug in a sarcoma subtype warrants further study.

9. Number of Participants With Tumors With Kinase Expression [Up to 37 weeks]

   Obtain tumor tissue for creation of tissue microarrays to examine the frequency of kinase expression such as SRC and/or FAK in leiomyosarcoma, liposarcoma, osteosarcoma, MFH, rhabdomyosarcoma, MPNST, chondrosarcoma, Ewing's, Alveolar soft part sarcoma (ASPS), chordoma, epithelioid sarcoma, giant cell tumor of bone, hemangiopericytoma, and GIST if activity of the drug in a subtype warrants further study. The outcome measure demonstrates the number of participants who had tissue that was able to generate tissue microarray for kinase expression.

10. Number of Participants With Tumors With Mutations in Kinases [Up to 37 weeks]

    Obtain tumor tissue to examine the frequency of mutations in kinases such as PDGFR in leiomyosarcoma, liposarcoma, osteosarcoma, MFH, rhabdomyosarcoma, MPNST, chondrosarcoma, Ewing's, ASPS, chordoma, epithelioid sarcoma, giant cell tumor of bone, hemangiopericytoma and GIST if activity of the drug in a subtype warrants further study. The outcome measure demonstrates the tissue that was able to generate tissue microarray for PDGFR analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Unresectable, recurrent, or metastatic histologically-confirmed soft tissue or bone sarcoma of one of the following subtypes:

• Leiomyosarcoma --* NO LONGER ELIGIBLE*

• Liposarcoma--* NO LONGER ELIGIBLE*

• Malignant fibrous histiocytoma (MFH)/pleomorphic undifferentiated sarcoma--* NO LONGER ELIGIBLE*

• Rhabdomyosarcoma --* NO LONGER ELIGIBLE*

• Malignant peripheral nerve sheath tumor (MPNST) --* NO LONGER ELIGIBLE*

• Osteosarcoma (skeletal or extraosseous)--* NO LONGER ELIGIBLE*

• Ewing's --* NO LONGER ELIGIBLE*

• Chondrosarcoma

• Alveolar soft part sarcoma

• Chordoma

• Epithelioid sarcoma

• Giant cell tumor of bone

• Hemangiopericytoma/solitary fibrous tumor

• Gastrointestinal Stromal Tumor (GIST) --* NO LONGER ELIGIBLE*

1. Documentation that subjects with leiomyosarcoma, liposarcoma, osteosarcoma, Ewing's, MPNST, rhabdomyosarcoma or MFH have received, not been eligible for or refused at least one prior chemotherapy regimen before participation in the dasatinib study. Subjects with GIST must have received or been intolerant to imatinib; prior treatment with other agents including sunitinib is not required.Neoadjuvant/adjuvant chemotherapy qualifies as prior therapy.

2. Subjects must have unidimensionally measurable lesion(s) either by x-ray, computed tomography (CT), magnetic resonance imaging (MRI) or physical examination documented within 30 days prior to registration.

3. Prior radiation will be allowed. More than two weeks should have elapsed since the administration of the last fraction of radiation therapy, and subjects must have recovered from grade 2 or higher associated toxicities. Measurable lesions, which are selected as target lesions, must be outside previously radiated fields or have documented progression no sooner than 6 weeks after completion of radiation.

4. More than 2 weeks must have elapsed since the subject has received any prior systemic chemotherapy (6 weeks for mitomycin C), and the patient should have recovered from toxicities to the baseline prior to the last course of chemotherapy.

5. Adequate hematologic function within 14 days prior to registration.

6. Prothrombin Time (PT) (or INR) and Partial Thromboplastin Time (PTT) ≤ 1.5 times the institutional upper limit of normal (ULN) within 14 days prior to registration.

7. Serum creatinine ≤ 2.0 times the institutional ULN within 14 days prior to registration.

8. Serum magnesium, potassium and adjusted (or ionized) calcium ≥ the institutional lower limit of normal (LLN). (Supplementation of electrolytes prior to screening is allowed).

9. Left ventricular ejection fraction ≥ 45% measured by echocardiogram or multiple gated acquisition (MUGA) within 30 days prior to registration (but must be performed after the last dose of an anthracycline) for subjects who have received an anthracycline (e.g. doxorubicin, epirubicin) or have a medical history of cardiac disease. The measurement of left ventricular ejection fraction is not required of subjects whom have not received cardiotoxic chemotherapy (e.g. anthracycline) and do not have a medical history of cardiac disease.

10. Sexually active women and men of childbearing potential must agree to use an effective method of birth control during the course of the study and for up to 3 months following the last dose of the study drug, in a manner such that risk of pregnancy is minimized. Surgical sterilization, intrauterine device or barrier method (e.g. condom and/or diaphragm with spermicidal agents) are acceptable forms of birth control.

11. Women of childbearing potential must have a negative pregnancy test (urine or serum) within 7 days prior to treatment. A pregnancy test is not required for registration. Women who have not menstruated for more than 2 years will be considered postmenopausal, thus not of childbearing potential.

12. Eastern Cooperative Oncology Group (ECOG) performance score 0, 1 or 2.

13. Weight ≥ 50 kg because there is limited experience with dasatinib in subjects weighing less than 50 kg.

14. ≥13 years of age Minors will be required to sign an assent document prior to treatment.

15. Subjects must be able to swallow whole tablets.

16. Subjects must be informed of the investigational nature of the study and provide written, informed consent and authorization to release protected health information using a document(s) approved by the investigator's institution.

17. A paraffin block, either from a previous surgery or recent biopsy, should be available for correlative studies. If a block of tumor is not available, at least 8 unstained slides of tumor sample, 1 H&E and three (3) 15 micron-thick sections in an eppendorf tube for DNA extraction from a representative portion of the sarcoma may be substituted after discussion with and approval from the study Principal Investigator.

Exclusion Criteria:

1. Subjects who are curable by conventional multidisciplinary management.

2. Subjects with symptomatic central nervous system metastasis.

3. Women who are pregnant or nursing/breastfeeding.

4. History of significant bleeding disorder unrelated to cancer, including:

• Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)

• Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)

1. Subjects currently taking medications that inhibit platelet function (i.e., aspirin, dipyridamole, epoprostenol, eptifibatide, clopidogrel, cilostazol, abciximab, ticlopidine, and any non-steroidal anti-inflammatory drug) because of a potential increased risk of bleeding from dasatinib.

2. Subjects currently taking anticoagulants (warfarin, heparin/low molecular weight heparin [e.g., danaparoid, dalteparin, tinzaparin, enoxaparin]) because of a potential increased risk of bleeding from dasatinib.

3. Diagnosis of unstable angina or myocardial infarction within 6 months of study entry.

4. Subjects currently taking one or more of the following drugs that are generally accepted to have a risk of causing Torsades de Pointes:

• Quinidine, procainamide, disopyramide

• Amiodarone, sotalol, ibutilide, dofetilide

• Erythromycins, clarithromycin

• Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide

• Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.

1. Diagnosed or suspected congenital long QT syndrome.

2. Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 450 msec) within 30 days prior to study registration.

3. Subjects unable or unwilling to suspend treatment with bisphosphonates for at least the first 8 weeks of treatment with study drug because of the risk of hypocalcemia caused by dasatinib.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
2	City of Hope	Duarte	California	United States	91010
3	Cedars-Sinai Outpatient Cancer Center	Los Angeles	California	United States	90048
4	Stanford University	Palo Alto	California	United States	94304
5	Sarcoma Oncology Center	Santa Monica	California	United States	90403
6	Washington Cancer Institute	Washington	District of Columbia	United States	20010
7	Winship Cancer Institute at Emory University	Atlanta	Georgia	United States	30308
8	Kootenai Cancer Center	Coeur d'Alene	Idaho	United States	83814
9	Oncology Specialists	Park Ridge	Illinois	United States	60068
10	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202
11	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
12	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland	United States	21231
13	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
14	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
15	University of Michigan	Ann Arbor	Michigan	United States	48109
16	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
17	Pennsylvania Oncology Hematology Associates	Philadelphia	Pennsylvania	United States	19106
18	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
19	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
20	MD Anderson	Houston	Texas	United States	77030

Sponsors and Collaborators

• Sarcoma Alliance for Research through Collaboration
• Bristol-Myers Squibb

Investigators

• Principal Investigator: Scott Schuetze, MD, PhD, University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• SARC Website

Publications

None provided.

• Responsible Party: Sarcoma Alliance for Research through Collaboration
• ClinicalTrials.gov Identifier: NCT00464620
• Other Study ID Numbers: SARC009
• First Posted: Apr 23, 2007
• Last Update Posted: Nov 23, 2018
• Last Verified: Oct 1, 2018

• Keywords provided by Sarcoma Alliance for Research through Collaboration: Dasatinib; Rhabdomyosarcoma; Malignant peripheral nerve sheath tumor; Chondrosarcoma; Ewing's; Alveolar soft part sarcoma (ASPS); Chordoma; Epithelioid sarcoma; Giant cell tumor of bone; Hemangiopericytoma/solitary fibrous tumor; Gastrointestinal Stromal Tumor (GIST)
• Additional relevant MeSH terms: Neoplasms; Sarcoma; Gastrointestinal Stromal Tumors; Rhabdomyosarcoma; Chondrosarcoma; Chordoma; Giant Cell Tumors; Nerve Sheath Neoplasms; Neurofibrosarcoma; Hemangiopericytoma; Solitary Fibrous Tumors; Bone Neoplasms; Giant Cell Tumor of Bone; Sarcoma, Ewing; Neuroectodermal Tumors, Primitive, Peripheral; Sarcoma, Alveolar Soft Part; Dasatinib

Study Results

Participant Flow

Recruitment Details	50 patients with GIST were enrolled between June 2008 and December 2009 and 48 were evaluable for response. Between May 2007 and May 2009, 200 patients with advanced, high-grade sarcoma were enrolled into the aggressive subtype for this study. 116 patients were registered beginning in July 2007 to the indolent subtype for this study.

Arm/Group Title	GIST: Dasatinib, 70 mg, Twice Daily	Aggressive Subtypes: Dasatinib, 70 mg, Twice Daily	Indolent Subtype: Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Period Title: Overall Study
STARTED	50	200	116
COMPLETED	48	198	109
NOT COMPLETED	2	2	7

Baseline Characteristics

Arm/Group Title	Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Overall Participants	359
Age (years) [Median (Full Range) ]
Aggressive subtype	52
GIST	60
Indolent	54
Sex: Female, Male (Count of Participants)
Female	96 26.7%
Male	104 29%
Female	19 5.3%
Male	31 8.6%
Female	33 9.2%
Male	76 21.2%
Race/Ethnicity, Customized (Count of Participants)
White	171 47.6%
Black	15 4.2%
Asian	6 1.7%
Other	6 1.7%
Unknown	2 0.6%
Native American	0 0%
White	41 11.4%
Black	3 0.8%
Asian	3 0.8%
Other	1 0.3%
Unknown	1 0.3%
Native American	1 0.3%
White	94 26.2%
Black	8 2.2%
Asian	3 0.8%
Other	4 1.1%
Unknown	0 0%
Native American	0 0%

Outcome Measures

1. Primary Outcome

Title	Response Rate: Number of Participants With Objective Tumor Response
Description	Assessment of objective tumor response for response rate with MRI or CT using Choi criteria: Complete Remission (CR) Complete disappearance of all measurable and evaluable disease for at least 4 weeks; Partial Remission (PR) A 10% or greater decrease from the baseline in the sum of the largest diameters of all measurable target lesions.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

116 subjects enrolled in the Indolent subtype, however 109 subjects began treatment. 50 patients enrolled in the GIST subtype, however 48 patients were evaluable. This explains the discrepancy between Overall Number of Participants Analyzed.

Arm/Group Title	GIST: Dasatinib, 70 mg, Twice Daily	Aggressive Subtypes: Dasatinib, 70 mg, Twice Daily	Indolent Subtype: Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants	48	198	109
Count of Participants [Participants]	12 3.3%	14 NaN	20 NaN

2. Primary Outcome

Title	6 Month Progression-free Survival Rate of "Indolent" Sarcomas Treated With Dasatinib
Description	Estimate the 6 month progression-free survival rate of "indolent" sarcomas treated with dasatinib. Progression is defined using Choi criteria, as a 10% or greater increase in the sum of all measurable target lesions over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or unequivocal reappearance of any lesion which had disappeared, or appearance of any new lesions of greater than double slice thickness in size, or any new or enlarging solid nodule in a previously hypodense treated mass.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Indolent Subtypes: Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants	109
Count of Participants [Participants]	52 14.5%

3. Primary Outcome

Title	6 Month Progression-free Survival Rate of Gastrointestinal Stromal Tumors (GIST)
Description	To estimate the 6 month progression-free survival rate of gastrointestinal stromal tumors (GIST). Progression is defined using Choi criteria, as a 10% or greater increase in the sum of all measurable target lesions over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or unequivocal reappearance of any lesion which had disappeared, or appearance of any new lesions of greater than double slice thickness in size, or any new or enlarging solid nodule in a previously hypodense treated mass.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GIST: Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants	48
Count of Participants [Participants]	14 3.9%

4. Secondary Outcome

Title	Median Time-to-progression of Subjects With GIST Treated With Dasatinib.
Description	To estimate the median time-to-progression of subjects with GIST treated with dasatinib.
Time Frame	Up to 30 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GIST: Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants	48
Median (Full Range) [months]	2.9

5. Secondary Outcome

Title	Overall Survival Rates at 2 and 5 Years From Registration of Subjects Treated With Dasatinib.
Description	To estimate the overall survival rates at 2 and 5 years from registration of subjects treated with dasatinib.
Time Frame	At 2 and 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GIST: Dasatinib, 70 mg, Twice Daily	Indolent Subtype: Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants	48	109
2 years overall survival	21 5.8%	48 NaN
5 years overall survival	8 2.2%	14 NaN

6. Secondary Outcome

Title	Median Time-to-progression of Subjects With "Indolent" Sarcomas Treated With Dasatinib.
Description	To estimate the median time-to-progression of subjects with "indolent" sarcomas treated with dasatinib.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Indolent Subtype: Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants	109
Median (Full Range) [months]	5.8

7. Secondary Outcome

Title	6 Month Progression-free Survival Rate of Subjects Enrolled in the Aggressive Subtype.
Description	To estimate the 6 month progression-free survival rate of subjects with leiomyosarcoma, liposarcoma, osteosarcoma including high-grade chondrosarcomas, Ewing's sarcoma, Malignant fibrous histiocytoma (MFH), rhabdomyosarcoma and MPNST treated with dasatinib.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

The numbers analyzed in one or more rows are different because they are broken up by cohorts.

Arm/Group Title	Aggressive Subtypes: Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants	198
UPS	6 1.7%
Leiomyosarcoma	5 1.4%
Osteosarcoma	5 1.4%
Rhabdomyosarcoma	0 0%
Ewing's Sarcoma	1 0.3%
Liposarcoma	0 0%
MPNST	0 0%

8. Secondary Outcome

Title	Median Time-to-progression of Subjects Enrolled in the Aggressive Subtype.
Description	To estimate the median time-to-progression of subjects with leiomyosarcoma, liposarcoma, osteosarcoma including high-grade chondrosarcomas, Ewing's sarcoma, MFH, rhabdomyosarcoma and MPNST treated with dasatinib.
Time Frame	Up to 37 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aggressive Subtypes: Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants	198
Median (Full Range) [months]	1.9

9. Secondary Outcome

Title	Overall Survival Rates at 2 and 5 Years From Registration of Subjects Enrolled in the Aggressive Subtype Treated With Dasatinib.
Description	To estimate the overall survival rates at 2 and 5 years from registration of subjects enrolled in the aggressive subtype treated with dasatinib.
Time Frame	At 2 and 5 years

Outcome Measure Data

Analysis Population Description

The number analyzed in one or more rows differs from overall number because the rows are broken down into cohorts. The counts in the categories will not add up to the number analyzed, because those numbers represent number of participants that have reached overall survival at 2 and 5 years.

Arm/Group Title	Aggressive Subtypes: Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants	198
Ewing's Sarcoma : 2 year overall survival rate	7 1.9%
Ewing's Sarcoma : 5 year overall survival rate	0 0%
Leiomyosarcoma : 2 year overall survival rate	21 5.8%
Leiomyosarcoma : 5 year overall survival rate	2 0.6%
Liposarcoma : 2 year overall survival rate	0 0%
Liposarcoma : 5 year overall survival rate	0 0%
MPNST : 2 year overall survival rate	0 0%
MPNST : 5 year overall survival rate	0 0%
Osteosarcoma : 2 year overall survival rate	15 4.2%
Osteosarcoma : 5 year overall survival rate	0 0%
Rhabdomyosarcoma : 2 year overall survival rate	8 2.2%
Rhabdomyosarcoma : 5 year overall survival rate	7 1.9%
UPS : 2 year overall survival rate	26 7.2%
UPS : 5 year overall survival rate	6 1.7%

10. Secondary Outcome

Title	Uni-dimensional and Bi-dimensional Tumor Size, Tumor Volumes and Tumor Average Density Determined by Computer-aided Automated Detection in a Subset of Subjects With Tumor Predominately Involving the Lung
Description	To prospectively collect uni-dimensional and bi-dimensional tumor size, tumor volumes and tumor average density determined by computer-aided automated detection in a subset of subjects with tumor predominately involving the lung
Time Frame	Up to 37 weeks

Outcome Measure Data

Analysis Population Description

This data was not collected because the imaging software and work station was not obtained.

Arm/Group Title	GIST: Dasatinib, 70 mg, Twice Daily	Aggressive Subtypes: Dasatinib, 70 mg, Twice Daily	Indolent Subtype: Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants	0	0	0

11. Secondary Outcome

Title	Plasma Level of Dasatinib and Inhibition of SRC and/or Focal Adhesion Kinase (FAK) in Peripheral Blood Mononuclear Cells
Description	Obtain blood samples to characterize plasma level of dasatinib and inhibition of SRC and/or FAK in peripheral blood mononuclear cells 2 hours after ingestion of drug at 2-4 weeks from the start of treatment if activity of the drug in a sarcoma subtype warrants further study.
Time Frame	2-4 weeks from start of treatment

Outcome Measure Data

Analysis Population Description

Evaluation of blood levels of drug was not performed because there was insufficient activity and the level of activity did not warrant further study.

Arm/Group Title	GIST: Dasatinib, 70 mg, Twice Daily	Aggressive Subtypes: Dasatinib, 70 mg, Twice Daily	Indolent Subtype: Dasatinib, 70 mg, Twice Daily
Arm/Group Description	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants	0	0	0

12. Secondary Outcome

Title	Number of Participants With Tumors With Kinase Expression
Description	Obtain tumor tissue for creation of tissue microarrays to examine the frequency of kinase expression such as SRC and/or FAK in leiomyosarcoma, liposarcoma, osteosarcoma, MFH, rhabdomyosarcoma, MPNST, chondrosarcoma, Ewing's, Alveolar soft part sarcoma (ASPS), chordoma, epithelioid sarcoma, giant cell tumor of bone, hemangiopericytoma, and GIST if activity of the drug in a subtype warrants further study. The outcome measure demonstrates the number of participants who had tissue that was able to generate tissue microarray for kinase expression.
Time Frame	Up to 37 weeks

Outcome Measure Data

Analysis Population Description

The overall number of participants analyzed demonstrates the number of participants whose tumor samples received. The results illustrate the tissue that was able to generate tissue microarray for SRC and FAK analysis.

Arm/Group Title	Osteosarcoma	Leiomyosarcoma	MFH/Undifferentiated Pleomorphic Sarcoma
Arm/Group Description	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants	32	44	37
Count of Participants [Participants]	11 3.1%	24 NaN	16 NaN

13. Secondary Outcome

Title	Number of Participants With Tumors With Mutations in Kinases
Description	Obtain tumor tissue to examine the frequency of mutations in kinases such as PDGFR in leiomyosarcoma, liposarcoma, osteosarcoma, MFH, rhabdomyosarcoma, MPNST, chondrosarcoma, Ewing's, ASPS, chordoma, epithelioid sarcoma, giant cell tumor of bone, hemangiopericytoma and GIST if activity of the drug in a subtype warrants further study. The outcome measure demonstrates the tissue that was able to generate tissue microarray for PDGFR analysis.
Time Frame	Up to 37 weeks

Outcome Measure Data

Analysis Population Description

The overall number of participants analyzed demonstrates the number of participants whose tumor samples were received. The results illustrate the tissue that was able to generate tissue microarray for PDGFR analysis.

Arm/Group Title	Osteosarcoma	Leiomyosarcoma	MFH/Undifferentiated Pleomorphic Sarcoma
Arm/Group Description	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
Measure Participants	32	44	37
Count of Participants [Participants]	11 3.1%	24 NaN	16 NaN

Adverse Events

Arm/Group Title	GIST, Aggressive, Indolent Subtypes
Arm/Group Description	Patients take 70 mg of Dasatinib, twice daily, for 28 day cycles Dasatinib: oral agent, continuous dosing, Cycles = 28 days
All Cause Mortality
	GIST, Aggressive, Indolent Subtypes
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	GIST, Aggressive, Indolent Subtypes
	Affected / at Risk (%)	# Events
Total	158/355 (44.5%)
Blood and lymphatic system disorders
Blood-other	1/355 (0.3%)	1
Cardiac disorders
Pericardial effusion	1/355 (0.3%)	1
Ventricular tachycardia	1/355 (0.3%)	1
Cardiac ischemia/infarction	1/355 (0.3%)	1
Congestive heart failure	2/355 (0.6%)	2
Atrial Fibrillation	2/355 (0.6%)	2
Gastrointestinal disorders
Colitis	4/355 (1.1%)	4
Constipation	4/355 (1.1%)	4
Diarrhea	8/355 (2.3%)	11
Distention	1/355 (0.3%)	1
Esophagitis	1/355 (0.3%)	1
Gastritis	1/355 (0.3%)	1
GI Hemorrhage: lower GI	2/355 (0.6%)	2
GI Hemorrhage: upper GI	2/355 (0.6%)	2
GI Obstruction: small bowel	6/355 (1.7%)	6
GI Obstruction: stomach	1/355 (0.3%)	1
GI Pain: abdomen	12/355 (3.4%)	12
GI Ulcer: colon	1/355 (0.3%)	1
GI- other	1/355 (0.3%)	1
Nausea	18/355 (5.1%)	20
Vomiting	17/355 (4.8%)	19
GI Hemorrhage- abdomen	1/355 (0.3%)	1
GI Hemorrhage- esophagus	1/355 (0.3%)	1
GI Hemorrhage- rectum	2/355 (0.6%)	2
GI Hemorrhage- stomach	1/355 (0.3%)	1
Pancreatitis	1/355 (0.3%)	1
General disorders
Constitutional symptoms-other	1/355 (0.3%)	1
Death, NOS	4/355 (1.1%)	4
Disease progression, NOS	7/355 (2%)	7
Fatigue	7/355 (2%)	7
Fever	15/355 (4.2%)	16
Flu-like syndrome	1/355 (0.3%)	1
Hemorrhage-other	2/355 (0.6%)	2
Pain	5/355 (1.4%)	5
Sudden death	1/355 (0.3%)	1
Multi-organ failure	1/355 (0.3%)	1
Rigors/chills	1/355 (0.3%)	1
Edema- limb	4/355 (1.1%)	4
Gait/walking	1/355 (0.3%)	1
Hepatobiliary disorders
Cholecystitis	1/355 (0.3%)	1
Immune system disorders
Allergic reaction	1/355 (0.3%)	1
Infections and infestations
Infection, Unk ANC: blood	2/355 (0.6%)	2
Infection-other	5/355 (1.4%)	6
Lung infection, 0-2 ANC: bronchus	1/355 (0.3%)	1
Lung Infection, 3-4 ANC: bronchus	1/355 (0.3%)	1
Lung Infection, Unk ANC: lung	1/355 (0.3%)	1
Injury, poisoning and procedural complications
Fracture	3/355 (0.8%)	3
Investigations
ALT	2/355 (0.6%)	4
Amylase	1/355 (0.3%)	1
AST	2/355 (0.6%)	2
Bilirubin	1/355 (0.3%)	1
Coagulation-other	1/355 (0.3%)	1
Creatinine	5/355 (1.4%)	5
Hemoglobin	14/355 (3.9%)	15
Leukocytes	1/355 (0.3%)	1
Neutrophils	2/355 (0.6%)	2
Platelets	1/355 (0.3%)	1
Lymphopenia	1/355 (0.3%)	1
Metabolism and nutrition disorders
Anorexia	4/355 (1.1%)	4
Dehydration	11/355 (3.1%)	11
Hyperkalemia	2/355 (0.6%)	2
Hyponatremia	5/355 (1.4%)	5
Hypokalemia	3/355 (0.8%)	3
Lipase	1/355 (0.3%)	1
Musculoskeletal and connective tissue disorders
Muscle weakness	6/355 (1.7%)	6
Musculo. Pain	17/355 (4.8%)	17
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	4/355 (1.1%)	4
Nervous system disorders
CNS hemorrhage	4/355 (1.1%)	4
Neuropathy- sensory	1/355 (0.3%)	1
Seizure	1/355 (0.3%)	1
Syncope	1/355 (0.3%)	1
Myelitis	1/355 (0.3%)	1
Ataxia	1/355 (0.3%)	1
Dizziness	1/355 (0.3%)	1
Headache	2/355 (0.6%)	2
Psychiatric disorders
Confusion	3/355 (0.8%)	3
Anxiety	1/355 (0.3%)	1
Renal and urinary disorders
GU Hemorrhage: urinary	2/355 (0.6%)	2
GU Hemorrhage: vagina	1/355 (0.3%)	1
GU Infection, 0-2 ANC: urinary tract	1/355 (0.3%)	1
GU Infection, Unk ANC: ureter	1/355 (0.3%)	1
GU Pain: kidney	1/355 (0.3%)	1
Incontinence, urinary	1/355 (0.3%)	1
Renal failure	5/355 (1.4%)	5
Urinary retention	1/355 (0.3%)	1
Renal failure	7/355 (2%)	7
Reproductive system and breast disorders
Reproductive pain: pelvis	1/355 (0.3%)	1
Pelvis pain	1/355 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	1/355 (0.3%)	1
Dyspnea	34/355 (9.6%)	37
Hypoxia	5/355 (1.4%)	5
Lung Pain	8/355 (2.3%)	8
Pleural effusion	30/355 (8.5%)	34
Pneumonitis	3/355 (0.8%)	3
Pulmonary-other	8/355 (2.3%)	9
Cough	2/355 (0.6%)	2
Skin and subcutaneous tissue disorders
Dermatology- other	1/355 (0.3%)	1
Rash	2/355 (0.6%)	2
Vascular disorders
Hypertension	1/355 (0.3%)	1
Hypotension	2/355 (0.6%)	2
Thrombosis/embolism	6/355 (1.7%)	6
Hypertension	2/355 (0.6%)	2
Hypotension	4/355 (1.1%)	4
Sweating	1/355 (0.3%)	1
Hematoma	1/355 (0.3%)	1
Other (Not Including Serious) Adverse Events
	GIST, Aggressive, Indolent Subtypes
	Affected / at Risk (%)	# Events
Total	314/355 (88.5%)
Blood and lymphatic system disorders
Thrombocytopenia	19/355 (5.4%)	31
Anemia	70/355 (19.7%)	103
Petechiae	1/355 (0.3%)	1
Lymph node pain	1/355 (0.3%)	1
Cardiac disorders
Palpaitations	2/355 (0.6%)	2
Prolonged QTc	4/355 (1.1%)	4
Pericardial effusion	4/355 (1.1%)	4
Cardiac- Other	4/355 (1.1%)	5
Atrial Tachycardia	1/355 (0.3%)	1
Sinus Bradycardia	1/355 (0.3%)	1
Ear and labyrinth disorders
Auditory/Ear- Other	1/355 (0.3%)	1
Eye disorders
Dry eye	1/355 (0.3%)	1
Blurred vision	1/355 (0.3%)	1
Diplopia	1/355 (0.3%)	1
Ocular- Other	4/355 (1.1%)	5
Eye pain	1/355 (0.3%)	1
Gastrointestinal disorders
Constipation	27/355 (7.6%)	27
Diarrhea	73/355 (20.6%)	99
Nausea	81/355 (22.8%)	93
Vomiting	36/355 (10.1%)	38
GI Pain: abdomen	15/355 (4.2%)	22
Heartburn	9/355 (2.5%)	10
Distention	3/355 (0.8%)	3
Dehydration	5/355 (1.4%)	5
Dry mouth	3/355 (0.8%)	3
Taste alteration	8/355 (2.3%)	8
Gastritis	3/355 (0.8%)	3
Dysphagia	4/355 (1.1%)	4
Ascites	1/355 (0.3%)	1
Flatulence	6/355 (1.7%)	6
Hemorrhoids	6/355 (1.7%)	9
Gastrointestinal- Other	7/355 (2%)	7
Mucositis	4/355 (1.1%)	4
Fistula	1/355 (0.3%)	1
GI Hemorrhage	9/355 (2.5%)	10
GI Pain	15/355 (4.2%)	22
General disorders
Edema	34/355 (9.6%)	50
Fatigue	113/355 (31.8%)	144
Fever	27/355 (7.6%)	29
Pain- Other	17/355 (4.8%)	17
Rigors/chills	16/355 (4.5%)	18
Flu-like syndrome	3/355 (0.8%)	3
Hepatobiliary disorders
Hepatic pain	1/355 (0.3%)	1
Immune system disorders
Allergic reaction	1/355 (0.3%)	1
Infections and infestations
Lung Infection	14/355 (3.9%)	16
GU Infection	4/355 (1.1%)	4
GI Infection	8/355 (2.3%)	11
Skin Infection	1/355 (0.3%)	1
Eye Infection	1/355 (0.3%)	1
Injury, poisoning and procedural complications
Bruising	2/355 (0.6%)	2
Wound complication	1/355 (0.3%)	1
Investigations
Weight loss	17/355 (4.8%)	17
Elevated PTT	3/355 (0.8%)	4
Leukopenia	13/355 (3.7%)	19
Neutropenia	15/355 (4.2%)	28
Lymphopenia	11/355 (3.1%)	12
Metabolism and nutrition disorders
Anorexia	45/355 (12.7%)	49
Hyperglycemia	25/355 (7%)	41
Hyponatremia	14/355 (3.9%)	18
Hypernatremia	1/355 (0.3%)	1
Elevated Alkaline phosphatase	15/355 (4.2%)	15
Elevated ALT	7/355 (2%)	9
Elevated AST	7/355 (2%)	10
Elevated serum bilirubin	2/355 (0.6%)	2
Elevated creatinine	11/355 (3.1%)	14
Hypoalbuminemia	5/355 (1.4%)	5
Hypokalemia	6/355 (1.7%)	6
Hyperkalemia	6/355 (1.7%)	6
Acidosis	1/355 (0.3%)	1
Hypoglycemia	2/355 (0.6%)	2
Low serum bicarbonate	2/355 (0.6%)	2
Hypocalcemia	7/355 (2%)	10
Hypercalcemia	3/355 (0.8%)	3
Hypermagnesemia	9/355 (2.5%)	10
Elevated lipase	1/355 (0.3%)	1
Hypophosphatemia	5/355 (1.4%)	7
Musculoskeletal and connective tissue disorders
Muscle weakness	7/355 (2%)	8
Musculoskeletal pain	67/355 (18.9%)	100
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor Pain	10/355 (2.8%)	11
Nervous system disorders
Headache	52/355 (14.6%)	68
CNS Hemorrhage	2/355 (0.6%)	2
Somnolence	1/355 (0.3%)	1
Seizure	1/355 (0.3%)	1
Cognitive disturbance	1/355 (0.3%)	1
Tremor	1/355 (0.3%)	1
Ataxia	1/355 (0.3%)	1
Involuntary movement	3/355 (0.8%)	3
Sensory neuropathy	8/355 (2.3%)	8
Leukoencephalopathy	1/355 (0.3%)	1
Dizziness	8/355 (2.3%)	10
Psychiatric disorders
Insomnia	8/355 (2.3%)	8
Confusion	4/355 (1.1%)	4
Agitation	3/355 (0.8%)	3
Anxiety	4/355 (1.1%)	5
Depression	7/355 (2%)	8
Renal and urinary disorders
Urinary incontinence	1/355 (0.3%)	1
Cystitis	1/355 (0.3%)	1
Urinary retention	2/355 (0.6%)	2
Urinary frequency	4/355 (1.1%)	4
Urine color change	1/355 (0.3%)	1
Bladder spasms	2/355 (0.6%)	2
Renal - Other	5/355 (1.4%)	5
Ureter obstruction	1/355 (0.3%)	1
GU Hemorrhage	3/355 (0.8%)	5
Reproductive system and breast disorders
Pelvis pain	4/355 (1.1%)	4
Breast pain	2/355 (0.6%)	2
Respiratory, thoracic and mediastinal disorders
Cough	45/355 (12.7%)	55
Dyspnea	56/355 (15.8%)	78
Pleural effusion	43/355 (12.1%)	60
Atelectasis	1/355 (0.3%)	1
Hypoxia	1/355 (0.3%)	1
Pneumonitis	1/355 (0.3%)	1
Voice alteration	4/355 (1.1%)	4
Pulmonary- Other	9/355 (2.5%)	12
Lung Pain	17/355 (4.8%)	18
Skin and subcutaneous tissue disorders
Rash	52/355 (14.6%)	64
Urticaria	1/355 (0.3%)	2
Pruritus	5/355 (1.4%)	5
Acne	3/355 (0.8%)	3
Hyperpigmentation	1/355 (0.3%)	1
Hypopigmentation	3/355 (0.8%)	3
Alopecia	2/355 (0.6%)	2
Skin pain	1/355 (0.3%)	1
Dermatology- Other	8/355 (2.3%)	9
Vascular disorders
Hypertension	5/355 (1.4%)	6
Hot flashes	3/355 (0.8%)	4
Sweating	8/355 (2.3%)	9
Flushing	5/355 (1.4%)	5
Phlebitis	1/355 (0.3%)	1
Thrombosis/embolism	1/355 (0.3%)	1
Vascular- Other	1/355 (0.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.